Use of Serum Clara Cell 16-kDa (CC16) Levels as a Potential Indicator of Active Pulmonary Fibrosis in Systemic Sclerosis

OBJECTIVE: To clarify the clinical significance of concentrations of serum Clara cell 16-kDa protein (CC16; previously denoted CC10) in the diagnosis and monitoring of pulmonary fibrosis (PF) in patients with systemic sclerosis (SSc); and to compare CC16 levels with levels of the current most reliable serum markers for PF, such as Krebs von den Lungen-6 (KL-6) antigen and surfactant protein-D (SP-D). METHODS: Serum levels of CC16, KL-6, and SP-D were determined by ELISA in 92 patients with SSc, 20 patients with systemic lupus erythematosus (SLE), and 20 healthy controls. In a retrospective longitudinal study, correlation of serum CC16 levels with the activity of PF was assessed in 16 SSc patients with PF. RESULTS: Although CC16 levels were higher in patients with SSc than in SLE patients or healthy controls, the difference was not significant. Increased serum CC16 levels were associated with involvement of PF, especially active PF, as well as KL-6 and SP-D. Receiver operating characteristic curve analysis revealed that the utility of CC16 is slightly inferior to KL-6, but was comparable with that of SP-D for detecting PF in patients with SSc. In the longitudinal study, serum levels of CC16, KL-6, and SP-D were significantly decreased in the inactive disease phase compared to the active disease phase. CONCLUSION: CC16 levels can be used as a potential serum biomarker for PF in addition to KL-6 and SP-D in patients with SSc.